Pharmacokinetics of Tacrolimus in Kidney Transplant Recipients: Twice Daily Versus Once Daily Dosing

Hardinger, Karen L.; Park, Jeong Mi; Schnitzler, Mark A.; Koch, Matthew J.; Miller, Brent W.; Brennan, Daniel C.

doi:10.1111/j.1600-6143.2004.00383.x

Cited by 49 publications

(46 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, dosing of MMF twice daily, instead of three times per day, may lead to increased adherence. Furthermore, a recent study reported that once-daily dosing of tacrolimus may provide safe and equivalent drug exposure to traditional twice-daily dosing, potentially increasing patient adherence (37). Admittedly, gastrointestinal side effects may preclude twice-daily dosing of MMF, and pharmacogenetic differences may preclude once-daily dosing of tacrolimus among blacks.…”

Section: Discussionmentioning

confidence: 99%

Race and Electronically Measured Adherence to Immunosuppressive Medications after Deceased Donor Renal Transplantation

Weng¹,

Israni²,

Joffe³

et al. 2005

Journal of the American Society of Nephrology

172

148

View full text Add to dashboard Cite

Nonadherence to immunosuppressive medications may partly explain the worse allograft outcomes among black recipients of renal transplants. In a prospective cohort study of recipients of deceased donor renal transplants, microelectronic cap monitors were placed on bottles of one immunosuppressive medication to (1) measure average daily percentage adherence during the first posttransplantation year and (2) determine the factors associated with adherence. A total of 278 transplant recipients who provided sufficient microelectronic adherence data were grouped into four categories of average daily percentage adherence: 95 to 100% adherence (41.0% of patients), 80 to 95% adherence (32.4%), 50 to 80% adherence (12.9%), and 0 to 50% adherence (13.7%). In the unadjusted ordinal logistic regression model, black race was associated with decreased adherence (odds ratio [

show abstract

Section: Discussionmentioning

confidence: 99%

Race and Electronically Measured Adherence to Immunosuppressive Medications after Deceased Donor Renal Transplantation

Weng¹,

Israni²,

Joffe³

et al. 2005

Journal of the American Society of Nephrology

172

148

View full text Add to dashboard Cite

show abstract

“…References retrieved from bibliographies were included if relevant to once-daily dosing of any formulation of tacrolimus, even if prior to the development of the modifiedrelease (MR) formulations (e.g. see Hardinger et al [5]). …”

Section: Methodsmentioning

confidence: 99%

“…Concentrations 12 h after the night-time dose of the immediate-release formulation are generally measured, and these morning trough concentrations have been used to develop the target concentration ranges for tacrolimus. There is diurnal variation in the concentration-time profile of tacrolimus, with peaks after the evening dose being lower and more prolonged [5,6].…”

Section: Introductionmentioning

confidence: 98%

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Staatz

Tett

2015

Clin Pharmacokinet

View full text Add to dashboard Cite

Tacrolimus is a pivotal immunosuppressant agent used in solid-organ transplantation. It was originally formulated for oral administration as Prograf(®), a twice-daily immediate-release capsule. In an attempt to improve patient adherence, retain manufacturer market share and/or reduce health care costs, newer once-daily prolonged-release formulations of tacrolimus (Advagraf(®) and Envarsus(®) XR) and various generic versions of Prograf(®) are becoming available. Tacrolimus has a narrow therapeutic index. Small variations in drug exposure due to formulation differences can have a significant impact on patient outcomes. The aim of this review is to critically analyse the published data on the clinical pharmacokinetics of once-daily tacrolimus in solid-organ transplant patients. Forty-three traditional (non-compartmental) and five population pharmacokinetic studies were identified and evaluated. On the basis of the stricter criteria for narrow-therapeutic-index drugs, Prograf(®), Advagraf(®) and Envarsus(®) XR are not bioequivalent [in terms of the area under the concentration-time curve from 0 to 24 h (AUC0-24) or the minimum concentration (C min)]. Patients may require a daily dosage increase if converted from Prograf(®) to Advagraf(®), while a daily dosage reduction appears necessary for conversion from Prograf(®) to Envarsus(®) XR. Prograf(®) itself, or generic immediate-release tacrolimus, can be administered in a once-daily regimen with a lower than double daily dose being reported to give 24-h exposure equivalent to that of a twice-daily regimen. Intense clinical and concentration monitoring is prudent in the first few months after any conversion to once-daily tacrolimus dosing; however, there is no guarantee that therapeutic drug monitoring strategies applicable to one formulation (or twice-daily dosing) will be equally applicable to another. The correlation between the tacrolimus AUC0-24 and C min is variable and not strong for all three formulations, indicating that trough measurements may not always give a good indication of overall drug exposure. Further investigation is required into whether the prolonged-release formulations have reduced within-subject pharmacokinetic variability, which would be a distinct advantage. Whether the effects of factors that influence tacrolimus absorption and pre-systemic metabolism (patient genotype status; gastrointestinal disease and disorders) and drug interactions differ across the formulations needs to be further elucidated. Most pharmacokinetic comparison studies to date have involved relatively stable patients, and many have been sponsored by the pharmaceutical companies manufacturing the new formulations. Larger randomized, controlled trials are needed in different transplant populations to determine whether there are differences in efficacy and toxicity across the formulations and whether formulation conversion is worthwhile in the longer term. While it has been suggested that once-daily administration of tacrolimus may improve patient compliance, further studies a...

show abstract

“…Because a significant relationship of higher dosing frequencies to decreased adherence has been demonstrated (3), once daily morning administration of twice-daily tacrolimus formulation (Prograf R ; Astellas Pharma, Tokyo, Japan; hereafter referred as Tac-BID) has been tried (7). Recently, a modified-release once-daily tacrolimus formulation (Advagraf R ; Astellas Pharma, Tokyo, Japan; hereafter referred as Tac-OD) has been developed to provide more convenient once daily dosing that may contribute to improve patient adherence to immunosuppressive medication and by inference, graft survival, compared with twicedaily tacrolimus formulation.…”

Section: Introductionmentioning

confidence: 99%

Conversion of Twice-Daily Tacrolimus to Once-Daily Tacrolimus Formulation in Stable Pediatric Kidney Transplant Recipients: Pharmacokinetics and Efficacy

Min

Kang

et al. 2013

American Journal of Transplantation

View full text Add to dashboard Cite

The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C 0 concentrations (4.10 AE 1.16-3.53 AE 1.10 ng/mL, p ¼ 0.004), and AUC 0-24 (151.8 AE 41.6-129.8 AE 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.

show abstract

Pharmacokinetics of Tacrolimus in Kidney Transplant Recipients: Twice Daily Versus Once Daily Dosing

Cited by 49 publications

References 16 publications

Race and Electronically Measured Adherence to Immunosuppressive Medications after Deceased Donor Renal Transplantation

Race and Electronically Measured Adherence to Immunosuppressive Medications after Deceased Donor Renal Transplantation

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

Conversion of Twice-Daily Tacrolimus to Once-Daily Tacrolimus Formulation in Stable Pediatric Kidney Transplant Recipients: Pharmacokinetics and Efficacy

Contact Info

Product

Resources

About